The development and progression of cancer is a multistep process involving accumulation of multiple genetic aberrations. Most notable among such aberrations is the loss of apoptotic responses that normally serve as built in checkpoints against the emergence of cell populations with dysfunctional traits or the acquisition of pro-survival mechanisms that override the apoptotic signals. The loss of apoptotic mechanisms often results in abridged response to cancer therapy. As such, alternate or combinatorial approaches that kill cancer cells and induce tumor regression are being actively pursued by researchers and physicians.
Especially difficult to treat are those cancers which are hormonally related and/or are metastatic cancers. These cancers include, e.g., prostate cancer, breast cancer and lung cancer. Melanoma is also difficult to treat and has a low survival rate relative to many other cancers.
An essential feature of anticancer strategies is the selective action against cancer cells, with little or no damage inflicted in normal cells. Nonetheless, side effects of cancer therapies are often severe. They include nausea, vomiting, pain, poor appetite, wasting, cachexia, diarrhea, burning in the stomach, stress, planter warts, nerve death-neuropathy, radiation burns, fatigue, constipation, anemia, anxiety, weakened immune system, dry skin, bone marrow suppression and hair loss. As such the identification of molecules that can specifically target tumor cells, with minimal or no adverse effects to normal cells constitutes a significant area of cancer research. Such molecules with selective action against tumor cells are valuable not only for their therapeutic potential; but also for their potential applications as tools for dissection of fundamental differences between normal and cancer cells. Thus, treatment methods that specifically target certain types of hormonally linked cancers would be extremely useful. Additionally, treatment methods that target cancers located in highly vascularized tissues such as for example lung, kidney, liver, or blood, and methods that target difficult to treat cancers, such as for example melanoma, would also be highly beneficial.